Synthesis and biological evaluation of novel 1-substituted 3-(3-phenoxyprop-1-yn-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors

被引：12
|
作者：
Zheng, Nan [1 ,2 ]
Hao, Qun [1 ]
Lin, Kuaile [1 ]
Pan, Jing [1 ,2 ]
Li, Yingxia [2 ]
Zhou, Weicheng [1 ]
机构：
[1] China State Inst Pharmaceut Ind, Shanghai Key Lab Antiinfect, State Key Lab New Drug & Pharmaceut Proc, Shanghai Inst Pharmaceut Ind, 285 Gebaini Rd, Shanghai 201203, Peoples R China
[2] Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 02期
关键词：
BTK inhibitors; 1-Substituted pyrazolo[3,4-d]pyrimidine; Inhibitory activity; B-cell lymphoblastic leukemia; Cytotoxicity; B-CELL; DISCOVERY; IBRUTINIB;
D O I：
10.1016/j.bmcl.2018.11.051
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new series of 1-substituted pyrazolopyrimidine derivatives were synthesized as potent BTK inhibitors and they were evaluated by enzyme-based assay and anti-proliferation against multiple B-cell lymphoma cell lines in vitro. Among these compounds, 9h exhibited the highest potency against BTK enzyme, with IC50 value of 4.2 nM. In particular, 8 and 9f performed better inhibition against the proliferation of B lymphoma cell lines DOHH2 and WSU-DLCL2 than the clinical drug ibrutinb. In addition, the test toward the normal PBMC cells showed that 8 possessed low cell cytotoxicity. All these explorations indicated that 8 could serve as a valuable anti-tumor agent for B-cell lymphoblastic leukemia treatment.
引用
收藏
页码：225 / 229
页数：5
相关论文
共 50 条
  • [31] Design, synthesis and evaluation of novel 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as potent, selective and reversible Bruton's tyrosine kinase (BTK) inhibitors for the treatment of rheumatoid arthritis
    Zhang, Chufeng
    Pei, Heying
    He, Jun
    Zhu, Jiali
    Li, Weimin
    Niu, Ting
    Xiang, Mingli
    Chen, Lijuan
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 169 : 121 - 143
  • [32] Design, synthesis and biological evaluation of novel 1, 3, 4-oxadiazole derivatives as potent neuraminidase inhibitors
    Yu, Wei
    Cheng, Li Peng
    Pang, Wan
    Guo, Ling Ling
    BIOORGANIC & MEDICINAL CHEMISTRY, 2022, 57
  • [33] Synthesis and Biological Evaluation of 1-Substituted (R)-6-(2'-Cyano-1'-Pyrrolidin-yl)-4-(3"-Hydroxyadamantan-1"-yl)-3-phenyl-1,2,4-triazines
    Markana, Keyur D.
    Patel, Megha A.
    Patel, Lavish H.
    Patel, Paresh S.
    INDIAN JOURNAL OF HETEROCYCLIC CHEMISTRY, 2023, 33 (04) : 431 - 438
  • [34] Design, synthesis and biological evaluation of novel 1H-indole-3-carbonitrile derivatives as potent TRK Inhibitors
    Xu, Shaoshan
    Jiang, Xiaosheng
    Xu, Mengdi
    Ai, Chengjian
    Zhao, Guanyi
    Jiang, Tao
    Liu, Yang
    Tian, Zhen
    Zhang, Meihui
    Dong, Jinhua
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2025, 285
  • [35] Design, synthesis, biological activity evaluation of 3-(4-phenyl-1H-imidazol-2-yl)-1H-pyrazole derivatives as potent JAK 2/3 and aurora A/B kinases multi-targeted inhibitors
    Zheng, You-Guang
    Wang, Jin-An
    Meng, Long
    Pei, Xin
    Zhang, Ling
    An, Lin
    Li, Cheng-Lin
    Miao, Ying-Long
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2021, 209
  • [36] Novel 3-substituted-1-aryl-5-phenyl-6-anilinopyrazolo[3,4-d]pyrimidin-4-ones: Docking, synthesis and pharmacological evaluation as a potential anti-inflammatory agents
    Yewale, Sandeep B.
    Ganorkar, Saurabh B.
    Baheti, Kamalkishor G.
    Shelke, Rupesh U.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (21) : 6616 - 6620
  • [37] Synthesis, Cytotoxicity, Antimicrobial and Docking Simulation of Novel Pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine Derivatives
    Hassaneen, Hamdi M.
    Saleh, Fatma M.
    Abdallah, Tayseer A.
    Mohamed, Magda F.
    Mohamed, Yasmin Sh
    Awad, Enas M.
    Abdelhamid, Ismail A.
    MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2019, 19 (08) : 657 - 670
  • [38] Design, synthesis, and biological evaluation of novel pyrazolo [3,4-d] pyrimidine derivatives as potent PLK4 inhibitors for the treatment of TRIM37-amplified breast cancer
    Sun, Yin
    Sun, Yu
    Wang, Lin
    Wu, Tianxiao
    Yin, Wenbo
    Wang, Jingkai
    Xue, Yanli
    Qin, Qiaohua
    Sun, Yixiang
    Yang, Huali
    Zhao, Dongmei
    Cheng, Maosheng
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2022, 238
  • [39] STUDIES ON ANNELATED 1,4-BENZOTHIAZINES AND 1,5-BENZOTHIAZEPINES .4. SYNTHESIS AND BIOLOGICAL-ACTIVITY OF NEW 1-SUBSTITUTED DERIVATIVES OF 4H-SYM-TRIAZOLO[3,4-C]-1,4-BENZOTHIAZINE AND 4,5-DIHYDRO-SYM-TRIAZOLO[3,4-D]-1,5-BENZOTHIAZEPINE
    AMBROGI, V
    GRANDOLINI, G
    PERIOLI, L
    DEMIA, GM
    RICCI, M
    TUTTOBELLO, L
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1991, 26 (08) : 835 - 838
  • [40] Synthesis and biological evaluation of 4-((3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)oxy)quinoline derivatives as novel potential transforming growth factor-(3 type 1 receptor inhibitors for hepatocellular carcinoma
    Liu, Siyuan
    Wang, Fusheng
    Zhang, Caifang
    Jiang, Hong
    Liu, Chun
    BIOORGANIC CHEMISTRY, 2025, 155
12345